lncRNA requirements for mouse acute myeloid leukemia and normal differentiation

A substantial fraction of the genome is transcribed in a cell type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures. Leukemia blasts show a myeloid differentiation phenotype when these lncRNAs were depleted, and our data indicates that this effect is mediated via effects on the c-MYC oncogene. Bone marrow reconstitutions showed that a lncRNA expressed across all progenitors was required for the myeloid lineage, whereas the other leukemia-induced lncRNAs were dispensable in the normal setting

A digital intake approach in specialized mental health care : study protocol of a cluster randomised controlled trial

Background: Enhancing patient participation is becoming increasingly important in mental health care as patients use to have a dependent, inactive role and nonadherence to treatment is a regular problem. Research shows promising results of initiatives stimulating patient participation in partnership with their clinicians. However, few initiatives targeting both patients’ and clinicians’ behaviour have been evaluated in randomised trials (RCT). Therefore, in GGz Breburg, a specialized mental health institution, a digital intake approach was developed aimed at exploring treatment needs, expectations and preferences of patients intended to prepare patients for the intake consultations. Subsequently, patients and clinicians discuss this information during intake consultations and make shared decisions about options in treatment. The aim of this trial is to test the efficacy of this new digital intake approach facilitated by Routine Outcome Monitoring (ROM), peer support and training of clinicians as compared to the intake as usual. The primary outcome is decisional conflict about choices in treatment. Secondary outcomes focus on patient participation, shared decision making, working alliance, adherence to treatment and clinical outcomes. Methods: This article presents the study protocol of a cluster-randomised controlled trial in four outpatient departments for adults with depression, anxiety and personality disorders, working in two different regions. Randomisation is done between two similar intake-teams within each department. In the four intervention teams the new intake approach is implemented. The four control teams apply the intake as usual and will implement the new approach after the completion of the study. In total 176 patients are projected to participate in the study. Data collection will be at baseline, and at two weeks and two months after the intake. Discussion: This study will potentially demonstrate the efficacy of the new digital intake approach in mental health care in terms of the primary outcome the degree of decisional conflict about choices in treatment. The findings of this study may contribute to the roll out of such eHealth initiatives fostering patient involvement in decision making about their treatment

Ентропійний аналіз макросистем без основного постулату статистичної механіки

It is shown that for most nonphysical macrosystems the basic postulate of statistical mechanics (the postulate of equal a priori probability of microstates) loses its power and the role of entropy should be fulfilled by a more general characteristic. Examples of distribution laws are considered.Показано, что для большинства нефизических макросистем основной постулат статистической механики (постулат равной априорной вероятности микросостояний) утрачивает силу и роль энтропии должна выполнять более общая характеристика. Рассмотрены примеры законов распределения.Показано, що для більшості нефізичних макросистем основний постулат статистичної механіки (постулат рівної апріорної імовірності мікростанів) втрачає силу, а роль ентропії має виконувати більш загальна характеристика. Розглянуто приклади законів розпділу

Diagnostic management of cheilitis. An approach based on a recent proposal for cheilitis classification

Currently, there are no clear recommendations for diagnostic management of lip inflammation and cheilitis, which is evident in the varied nomenclature and subtypes found in medical literature on cheilitis. This can confound diagnostic management. We therefore recently put forth a proposal for cheilitis classification, defining three groups of cheilitis based on duration and etiology: mainly reversible cheilitis, mainly irreversible cheilitis, and cheilitis connected to other diseases. The most common forms of cheilitis are the reversible types, usually of short duration and commonly easily resolved or treated. In contrast, irreversible types of cheilitis are rare, are harder to treat, and are confirmed only after a biopsy of an inflamed lesion. To correctly diagnose and manage the different types, practitioners must consider several factors, including visible manifestations of the disease, related diseases and symptoms, personal habits, weather conditions, allergies, nutritional deficiencies, and results from tissue swabs and biopsies. In addition, multispecialty collaboration and communication involving dermatology, oral pathology, clinical immunology, otorhinolaryngology, rheumatology, and other fields can be crucial for patient outcome. We believe our classification system would be of great benefit to researchers, patients, and doctors by simplifying both nomenclature and disease recognition, thus ensuring timely and adequate treatment

Breast implant-associated anaplastic large cell lymphoma: two distinct clinicopathological variants with different outcomes.

ALK-negative anaplastic large cell lymphoma associated with breast implant (i-ALCL) has been recently recognized as a distinct entity. Among 43 830 lymphomas registered in the French Lymphopath network since 2010, 300 breast lymphomas comprising 25 peripheral T-cell lymphomas (PTCL) were reviewed. Among PTCL, ALK-negative ALCL was the most frequent and all of them were associated with breast implants. Since 2010, all i-ALCL cases were collected from different institutions through Lymphopath. Immuno-morphologic features, molecular data and clinical outcome of 19 i-ALCLs have been retrospectively analyzed. The median age of the patients was 61 years and the median length between breast implant and i-ALCL was 9 years. Most implants were silicone-filled and textured. Implant removal was performed in 17 out of 19 patients with additional treatment based on mostly CHOP or CHOP-like chemotherapy regimens (n = 10/19) or irradiation (n = 1/19). CHOP alone or ABVD following radiation without implant removal have been given in two patients. The two clinical presentations, i.e. effusion and less frequently tumor mass correlated with distinct histopathologic features: in situ i-ALCL (anaplastic cell proliferation confined to the fibrous capsule) and infiltrative i-ALCL (pleomorphic cells massively infiltrating adjacent tissue with eosinophils and sometimes Reed-Sternberg-like cells mimicking Hodgkin lymphoma). Malignant cells were CD30-positive, showed a variable staining for EMA and were ALK negative. Most cases had a cytotoxic T-cell immunophenotype with variable T-cell antigen loss and pSTAT3 nuclear expression. T-cell receptor genes were clonally rearranged in 13 out of 13 tested cases. After 18 months of median follow-up, the 2-year overall survival for in situ and infiltrative i-ALCL was 100% and 52.5%, respectively. In situ i-ALCLs have an indolent clinical course and generally remain free of disease after implant removal. However, infiltrative i-ALCLs could have a more aggressive clinical course that might require additional therapy to implant removal